DE2360202C2 - Process for the preparation of 4-chloro-benzothiazole compounds - Google Patents

Description

ACW.B

or

/ ?, OCH, CN

wherein A represents a halogen atom, B has the meanings given above and /?, represents an alkanesulfonyl group or an arylsulfonyl group, in the presence of an alkaline condensing agent and , if desired, converting the group B into the carboxyl group or its salts or esters, characterized in that as inert, water-immiscible solvent in the diazotization of 2-amino-4-chlorobenzothiazole hydrohalide an aliphatic halogenated hydrocarbon in which the main products of the diazotization reaction are at least 10% (weight / volume) soluble at 20 ° C.

2. The method according to claim 1, characterized in that the solvent used is ethylene dichloride used.

The compound 4-chloro-2-oxobenzothiazolin-3-ylacetic acid (often called benazolin) and its esters and salts are widely used as herbicides. Typical salts are the alkali metal salts, for example the sodium or preferably potassium salts and amine salts, for example the triethylamine or diethanolamine or, preferably, dimethylamine salts. Typical esters are the C _1-7 alkyl esters, for example the methyl, isopropyl or, preferably, ethyl esters. Benazolin and its esters and salts are first described in GB-PS 8 62 226. The process described there for their preparation consists in reacting 4-chloro (or 4-bromo) - 2-oxobenzothiazoline (also known as 4-chloro-2-hydroxybenzothiazole) with a compound which supplies the acetic acid part, for example Ethyl bromoacetate. According to a further process described in this patent, 2-oxobenzolhiazolin-3-ylacetic acid is chlorinated or brominated. The process first described has generally been technically most satisfactory, but suffers from the fact that it has been difficult to date. to obtain the necessary starting material in sufficiently high yield and purity.

4-Chior-2-hydroxybenzothiazole can according to Elderfield and Short (J. Org. Chem. 1953 18 1092) after a Process can be prepared in which 2-amino-4-chlorobenzothiazole in a mixture of s bromine and hydrobromic acid diazotized to form 2-bromo-4-chlorobenzothiazole, and thereafter hydrolyzes this to form the desired product. The yields obtained were 72% in the first and 77% in the second stage, which results in a

in overall yield of 56% in the production of 4-chloro-2-hydroxybenzothiazole yields from 2-amino-4-chlorobenzothiazole. The procedure was for that technical production not very satisfactory.

In GB-PS 9 66 496 processes are described by means of which 2-amino-4-chlorobenzothiazole in 2,4-dichlorobenzothiazole in high yield and this in turn could convert into 4-chloro-2-hydroxylbenzothiazole with high yield, whereby one a fairly satisfactory overall yield, of

2 (i receives at least 80%. The procedure consists of that 2-amino-4-chlorobenzothiazole is diazotized in hydrochloric acid and then the dichloro compound is hydrolyzed. In the patent it is stated that the reaction by the presence of a water-miscible Solvent can be facilitated, and that particularly desirable conditions are then obtained when benzene or toluene is used, with bezene giving the most satisfactory results would. The duration of the diazotization was long, e.g. B.

3d over 16 hours.

Modification of this process has been used extensively on an industrial scale. This modified method is that 2-amino-4-chlorobenzothiazole hydrobromide in a mixture of 2,4-dichlorobenzothiazole and 2-bromo-4-chlorobenzothial converts, and the mixture under Hydrolyzed formation of 4-chloro-2-hydroxybenzothiazole. The overall yields are around 70-80% by means of obtained with this process are essential

4 (i borrowed better than the previous yields of 56%, but the process, carried out on a technical scale, leaves a few wishes unfulfilled. It's been a long time Reaction times required to obtain these yields. 4-chloro-2-hydroxybenzothiazole is also used contaminated with significant amounts of unacceptable by-products which are removed must, generally at a later stage in the overall process for making benazolin or its esters or salts. This means an additional cleaning stage which is of course time consuming and is expensive, and which one would like to avoid. Furthermore, the formation of these is undesirable By-products a waste of raw material.

The invention relates to an improved process for the preparation of 4-chloro-benzothiazole compounds of the general formula I.

Mil H

wherein B denotes a carboxy group or a salt thereof, an ester, amide or a nitrile group, hydrolysis by diazotizing 2-amino-4-chlorobenzothiazole hydrohalogenide in the presence of an inert, water-immiscible solvent

of the product obtained to 4-chloro-2-hydroxybenzothiazole and its condensation with a compound of the general formulas

/JCH.S

or

Zf ₁ OCH ₁ CN

wherein A represents a halogen atom, B has the meanings given above and R _{1 represents} an alkanesulfonyly group or an arylsulfonyl group, in the presence of an alkaline condensing agent | ₍ > by means of and, if desired, converting group B into the carboxyl group or its salts or esters.

It has surprisingly been found that improved purity and improved yield and / or shorter reaction time actually obtained by ₅ may be that one particular, water-immiscible solvent used for the diazotization. It is therefore now possible to produce benazolin and its esters and salts in such a high degree of purity that impurities are only present in such small amounts and in such a way that it is no longer essential to carry out the above-mentioned purification step. Furthermore, it is now possible, with the same reaction times as were used in the previous processes, to obtain better yields than were previously available or to obtain satisfactory yields in much shorter reaction times than could previously be used with formation of satisfactory yields, and / or reduce the waste of raw material.

According to the invention, the above object is achieved in that one is inert, not with water a miscible solvent in the diazotization of 2-amino-4-chlorobenzothiazole hydrohalide aliphatic halocarbon in which the main products of the diazolation reaction to at least 10% (weight / volume) soluble at 20 ° C are used.

The main products of the diazotization reaction are 2-halo-4-chlorobenzothiazoles. When 2-amino-4-chlorobenzothiazole is used in the form of the hydrobromide, the main product is 2-bromo-4-chlorobenzothiazole. 2,4-dichlorobenzothiazole can also be used.

The preferred aliphatic halogenated hydrocarbons which are used according to the invention are chlorinated hydrocarbons, for example ethylene dichloride, which is particularly preferred, Methylene chloride, chloroform, carbon tetrachloride, tetrachloroethane, trichlorethylene, perchlorethylene, 1,2-dichloropropane and 1,1,1-trichloroethane. Other halogenated hydrocarbons include the bromine-containing hydrocarbons, for example Ethylene dibromide. Solvents with a boiling point between 60-90 ° C are preferred used.

The diazotization reaction is preferably carried out at a temperature below 30 ° C, e.g. B. at 20-25 ° C, usually in hydrochloric acid with a higher concentration than IN, preferably between 5.5 and 6.5N carried out. The reaction is also preferably carried out in the presence of acetic acid. the The amount of organic solvent is not critical, but is preferably at least 20% by volume. (> 5 based on the total reaction mixture, for example 25-60% by volume.

The diazotization reaction will generally

at least 2 hours, but often less than 7 or 5 hours. It is generally continued until essentially no solid material remains suspended in the aqueous phase. The organic phase is then separated and preferably evaporated to dryness before being hydrolyzed. The hydrolysis can be carried out in such a way that it is reacted with a mineral acid, for example concentrated hydrochloric acid, preferably in the presence of a water-miscible solvent, for example methanol, ethanol or denatured alcohol. The hydrolysis is expediently carried out at a temperature of 50-150 ° C., and preferably under reflux. The product can be isolated using conventional methods and then converted into the 4-chloro-benzothiazole compounds mentioned in accordance with the teaching of GB-PS 9 66 496. This second process step consists in treating the 4-chloro-2-hydroxybenzothiazole with a compound of the formula ACH ₁ B or /? | OCH ₂ CN, in which A is a halogen atom, B is a carboxyl group or a salt, ester, amide or nitrile thereof and / ?, an alkanesulfonyl or arylsulfonyl group, is condensed in the presence of an alkaline condensing agent, whereby a compound of the formula I is obtained.

and if desired converts the radical B into the carboxyl group or its salts or esters.

In addition to the advantages that you get high yields and faster reaction times than below Use of the solvents described so far was available, the use of halogenated aliphatic hydrocarbons as a solvent according to the invention have a further significant advantage. This consists in producing 2-amino-4-chlorobenzothiazole hydrohalide thereby can that one N-2-chlorophenylthiourea in the same organic solvent system. As it for the subsequent diazotization reaction is used, with the result cyclized. that this 2-Amino-4-chlorobenzothiazole hydrohalide prepared and in the same organic solvent system can be implemented without this having to be isolated before the diazotization stage. Through this, avoiding the separation of the compound before the diazotization increases the overall yield and the total time taken to complete the preparation of benazolin from N-2-chlorophenylthiourea is required, further improved.

The preferred conditions for cyclizing the N-2-chlorophenylthiourea to produce 2-Amino-4-chlorobenzothiazole hydrohalide, consists in that the thiourea with a Source of chlorine or bromine atoms in a halogenated aliphatic hydrocarbon solvent, as described above. The preferred source of chlorine atoms is sulfuryl chloride, while the preferred source of bromine atoms is bromine. The reaction temperature is preferable 30-100 ° C.

The invention is illustrated in the following examples, in which the "percentages" refer to the

Refer to »weight«. The yields relate to the pure substance, so the actual yields (of contaminated material) are slightly higher than indicated.

Example la

2-Amino-4-chlorobenzothiazole hydrobromide (79 g) and ethylene dichloride (300 ml) became a suppurative mixture of concentrated hydrochloric acid (114 ml), glacial acetic acid (78 ml) and water (114 ml) in a 1 liter flask in given. The whole mixture was stirred and kept at 20-25 ° C with water cooling while a solution. Sodium nitrite (41 g) in water (67 ml) at a constant rate during 2 hours was added. The mixture ι? was stirred for a further 2 hours. Water (100 ml) was added and the lower layer separated and evaporated to dryness. The residue was in dissolved in hot denatured alcohol and the solution kept under rapid reflux and stirred, wäh- zn concentrated hydrochloric acid (182 ml) was added over 2½ hours. The stirring and heating continued for another 2 hours. The mixture was then cooled below 30 ° C and water (182 ml) admitted. The solid was collected, washed acid free and dried under vacuum at 60 ° C. The 4-chloro-2-hydroxybenzothiazole obtained in this way had after titration with tetrabutylammonium hydroxide in acetone a purity of 95%. Yield = 83%.

Example Ib

4-chloro-2-hydroxybenzothiazoI (185.5 g) that was obtained according to Example 1 a, was with anhydrous Potassium carbonate (138.5 g), sodium iodide (5 g) and methyl ethyl ketone (1 liter) mixed. The mixture was stirred and refluxed while adding ethyl chloroacetate (135 g). That The mixture was refluxed for an additional 4 hours, water (280 ml) added and the mixture cooled to 70 ° C. The aqueous layer was discarded and the organic layer evaporated, whereby an oil was obtained which was dissolved in denatured spirit (200 ml) under reflux. Watery Sodium hydroxide (2.5N, 440 ml) was added and reflux continued for 1/2 hour. The solution was then cooled and acidified to pH 1-2 with hydrochloric acid. The product obtained was filtered off, washed with water and dried to form benazolin; Melting point 185 18X ° C.

Example 2

Example 1a was repeated, with an equivalent volume of methylene chloride instead of ethylene dichloride was used. The 4-chloro-2-hydroxybenzothiazole thus obtained had a purity of 95%. Yield = 87%.

Example 3
N-2-chlorophenylthiourea (65 g) was added to a mixture of glacial acetic acid (48 ml) and ethylene dichloride (195 ml) in a 1 liter flask. The mixture was stirred vigorously and bromine (61.5 g) was added in one portion. When the temperature stopped rising, the mixture was refluxed for 4 hours. It was then cooled to a temperature between 15 and 20 ° C and a mixture of concentrated hydrochloric acid (115 ml) and water (115 ml) was added. The temperature was maintained at 20-25 ° C while a solution of sodium nitrite (41 g) in water was added over 2 hours. The experiment was then continued as described in Example 1a, whereby 4-chloro-2-hydroxybenzothiazole was obtained with a purity of 95%. Yield = 83%.

Examples 4-9

Example 1 a was repeated, but instead of ethylene dichloride equivalent volume of Chloroform (example 4), Tel räch lorä'i hy len (example 5). 1,1,1-trichloroethane (Example 6). 1,2-dichloropropane (Example 7), ethylene dibromide (Example 8) and twice the equivalent volume of carbon tetrachloride (Example 9) was added. The obtained 4-chloro-2-hydroxybenzothiazole had in each of these examples a purity in the range of 93 to 95% and provided yields of 73%. and 66%, respectively. 65%, 72%. 61% and 71%. Higher yields can be obtained by using the diazotization performs over a longer period of time.

Example 10

A slurry of N-2-chlorophenylthiourea (65 g) in a mixture of glacial acetic acid

(48 ml) and ethylene dichloride (36 ml) became slow with stirring to a solution of bromine (61.5 g) in ethylene dichloride (97 ml) added, while the Temperature was kept below 55 ° C with water cooling. The mixture was carefully refluxed

Heated for 4n and kept at this temperature for 4 hours. It was then cooled to 15 to 20 ° C and the experiment continued as in Example 3, thereby producing 4-chloro-2-hydroxybenzothiazole with a purity received by 95%. Yield = 84%.

Comparative example

Example 1a was repeated except that benzene was added instead of ethylene dichloride the addition of sodium nitrite over a period of 5 hours

> o instead of 2 hours and the stirring 16 Hours instead of 2 hours. 4-chloro-2-hydroxybenzothiazoI was in 77% Yield obtained and had a purity of only 87%, with 8.3% 4-chloro-2-phenylbenzothiazole was contaminated, which is difficult to separate at this stage. If the product is in Benazolin, as described in Example 1b, was converted, it was necessary to remove this impurity by extraction with methylene chloride after the hy-

to remove drolysis with sodium hydroxide.

Claims (1)

Patent claims: 1. Process for the preparation of 4-chloro-benzothiazole compounds of the general formula I. wherein B represents a carboxyl group or a salt thereof, an ester, an amide or a nitrile group, by diazotizing 2-amino-4-chlorobenzothiazole hydrohalide in the presence of an inert, water-immiscible solvent, hydrolysing the product obtained to 4-chlorine -2-hydroxybenzothiazole and its condensation with a compound of the general formulas